Proliferative diabetic retinopathy is a major cause of blindness in the U.S. Glial cells are an integral component of retinal neovascularization associated with diabetes mellitus. Their precise role in the neovascular process is unknown. Specific questions posed in this application are: 1) How are retinal glia involved in membranes from diabetic patients? Do glial cells participate in the development of the posterior vitreous detachment in these patients?; 2) In an experimental model of retinal neovascularization can the early changes in the glio-vascular relationships be established?; and 3) Do retinally derived glial cells in culture produce substances which can stimulate vascular endothelial and other cells to migrate and proliferate? Is the release of these substances altered by hypoxia and hyperglycemia? The glia cell morphology in both the human tissues and animal model will be studied by a combination of light and electron microscopy as well as immunocytochemical methods. Any soluble factors released by glial cells will be studied by measuring stimulation of migration and proliferation of vascular endothelial and other cells. The results of these studies will lead to a better understanding of mechanisms involved in the formation of fibrovascular membranes in proliferative diabetic retinopathy. If retinal glia are essential in the development of neovascularization then specifically directed new treatment avenues could be pursued.